The transdermal route of parenteral drug delivery provides many advantages. Unfortunately, many drugs which are candidates for transdermal delivery have a tendency to cause skin irritation or sensitization, particularly when they are maintained in contact with the skin under occlusion for sustained periods of time. These drugs can cause undesirable skin reactions, such as itching and erythema. Therefore, despite the development of the transdermal drug delivery art, there remains a continuing need for an improved method of overcoming irritation or sensitization caused by transdermal delivery of an irritating/sensitizing drug.
Skin irritation can be caused by a variety of factors including, but not limited to, physical factors (e.g., chafing or occluding the skin in an airtight manner), exposure to certain chemicals, exposure to pH outside the normal range of the skin or mucosa, and bacterial overgrowth. Generally, tissue irritation is the manifested result of damage or toxicity to cells in the skin or mucosa caused by their response to a cytotoxic (i.e., irritating) agent.
Skin sensitization is a two-phase process involving distinct biological mechanisms of the human immune system. The first phase is called the induction phase. Induction occurs when the skin of an individual is first exposed to the sensitizing drug. Generally, no visible skin reaction is noted during the induction phase. Following induction, some of the individual's lymphocytes are specifically sensitized to the drug. The second phase of sensitization is called elicitation. Elicitation occurs when the individual is subsequently (i.e., after induction) exposed to the same sensitizing drug. Elicitation causes a skin reaction to occur. The skin reaction occurring during elicitation is known as contact dermatitis.
This invention is directed towards either 1) preventing or reducing the irritation caused by an irritating drug or 2) preventing or reducing sensitization from occurring, as well as reducing or eliminating pain and discomfort occurring during the elicitation phase after sensitization has already been induced.